title: Whole-genome methylation sequencing reveals distinct impact of differential methylations on gene transcription in prostate cancer.
abstract: DNA methylation is one of the most important epigenetic mechanisms in regulating gene expression. Genome hypermethylation has been proposed as a critical mechanism in human malignancies. However, whole-genome quantification of DNA methylation of human malignancies has rarely been investigated, and the significance of the genome distribution of CpG methylation is unclear. We performed whole-genome methylation sequencing to investigate the methylation profiles of 13 prostate samples: 5 prostate cancers, 4 matched benign prostate tissues adjacent to tumor, and 4 age-matched organ-donor prostate tissues. Alterations of methylation patterns occurred in prostate cancer and in benign prostate tissues adjacent to tumor, in comparison with age-matched organ-donor prostates. More than 95% alterations of genome methylation occurred in sequences outside CpG islands. Only a small fraction of the methylated CpG islands had any effect on RNA expression. Both intragene and promoter CpG island methylations negatively affected gene expression. However, suppressions of RNA expression did not correlate with levels of CpG island methylation, suggesting that CpG island methylation alone might not be sufficient to shut down gene expression. Motif analysis revealed a consensus sequence containing Sp1 binding motif significantly enriched in the effective CpG islands.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Yan P
authors.initials: YP
authors.lastname: Yu
authors.affiliation: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Serena G
authors.initials: SG
authors.lastname: Liao
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Ren
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Amantha
authors.initials: A
authors.lastname: Michalopoulos
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: George
authors.initials: G
authors.lastname: Michalopoulos
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Joel
authors.initials: J
authors.lastname: Nelson
authors.affiliation: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: George C
authors.initials: GC
authors.lastname: Tseng
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address: luoj@msx.upmc.edu.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Luo
mesh_terms: D000368:Aged; D018899:CpG Islands; D019175:DNA Methylation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic